Electrically driven rabbit left atria were exposed to 20 min periods of hypoxia in the presence and absence of dimethyl sulfoxide (DMSO) or sucrose. Contractile strength declined significantly less than control when tissues were exposed to DMSO during hypoxia. On reoxygenation tissues treated with DMSO recovered pre-hypoxia contractile strength more slowly. Sucrose did not protect tissues during hypoxia. Comparison of results with DMSO and sucrose indicated that tissue depression prior to hypoxia could not explain the action of DMSO. Kinetic analysis performed on tension decline which occurred during hypoxia showed that two components were involved; rate of tension loss in both components was decreased by DMSO and there was a shift in the percentage of decline to the slower component. These data indicate that DMSO may increase energy availability, increase efficiency of energy utilization, or possibly affect the shift from aerobic to anaerobic metabolism during hypoxia, but not during the post-hypoxic recovery period.